A Study to Evaluate Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)

Official Title

A Phase II/III Multicentre Study Evaluating the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Somatic Mutations Detected in Blood (B-FAST: Blood-First Assay Screening Trial)

Summary:

This is a phase 2/3, global, multicentre, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic NSCLC determined to harbor oncogenic somatic mutations or positive by tumour mutational burden (TMB) assay as identified by two blood-based next-generation sequencing (NGS) circulating tumour DNA (ctDNA) assays.

Trial Description

Primary Outcome:

• Cohort A: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the Response Evaluation Criteria in Solid Tumours (RECIST) Version (v) 1.1
• Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1
• Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on RECIST v1.1 in bTMB PP1
• Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1
• Cohort E: Time in Response (TIR) as Assessed by the Investigator Based on RECIST v1.1
• Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1

• All Cohorts: Duration of Response (DOR) as Assessed by the Investigator Based on RECIST v1.1
• Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by the Investigator Based on RECIST v1.1
• Cohorts A, B, D, F: PFS as Assessed by the Investigator Based on RECIST v1.1
• All Cohorts: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on RECIST v1.1
• Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by IRF Based on RECIST v1.1
• All Cohorts: PFS as Assessed by IRF Based on RECIST v1.1
• All Cohorts: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on RECIST v1.1
• All Cohorts: Overall Survival (OS)
• All Cohorts: Percentage of Participants with Adverse Events (AEs)
• Cohorts A, B, D, E, F: Percentage of Participants with Improvement Compared with Baseline in Total Severity Symptom Score as Measured by Symptoms in Lung Cancer (SILC) Scale in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain)
• All Cohorts: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by the SILC Scale
• Cohorts C, E, F: Change from Baseline in Patient-Reported Lung Cancer Symptom (Cough, Dyspnea, Chest pain) Score as Measured by the SILC Scale
• All Cohorts: Change from Baseline in Health Related Quality of Life (HRQoL) Scores as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30)
• Cohorts A, B, D, E, F: Change from Baseline in HRQoL Scores as Measured by the SILC Scale
• All Cohorts: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the EORTC QLQ-C30
• Cohorts A, B, D, E, F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the SILC Scale
• All Cohorts: Health Status Assessed as an Index Score Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
• Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
• Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib
• Cohort B: Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of Alectinib
• Cohort B: Time to Reach Cmax (Tmax) of Alectinib
• Cohort B: Half-Life (t1/2) of Alectinib
• Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last
• Cohort B: Metabolite to Parent Exposure Ratio for Cmax
• Cohort C: Percentage of Participants with Objective Response as Assessed by the Investigator Based on RECIST v1.1
• Cohort C: Percentage of Participants Free from Disease Progression as Assessed by the Investigator Based on RECIST v1.1 at Months 6 and 12
• Cohort C: PFS as Assessed by the Investigator based on RECIST v1.1 in bTMB PP2
• Cohort C: OS in bTMB PP2
• Cohort D: Time to CNS progression as Assessed by the Investigator Based on RECIST v1.1
• Cohort D: Time to CNS progression as Assessed by the IRF Based on RECIST v1.1
• Cohorts D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-C30
• Cohorts D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-BN20
• Cohort D: Mean Plasma Concentration of Entrectinib
• Cohort D: Mean Plasma Concentration of Entrectinib Metabolite M5
• Cohort E: TIR as Assessed by the Investigator Based on RECIST v1.1
• Cohort E: TIR as Assessed by IRF
• Cohorts E, F: Serum Concentration of Atezolizumab
• Cohort E, F: Change from Baseline in Anti-Drug Antibodies (ADAs)

View this trial on ClinicalTrials.gov